Dietary pattern analysis has recently emerged as an important new direction in nutritional epidemiology. Although our work in current grant cycle has demonstrated the importance of major dietary patterns in predicting long-term risk of CVD, many theoretical and methodological issues remain unsettled. Also, as type 2 diabetes reaches epidemic proportions in the US and worldwide, it becomes urgent to evaluate various dietary patterns (including current dietary recommendations) and overall diet quality in relation to the development of diabetes. In this competing renewal, we will apply novel statistical methods (such as confirmatory factor analysis and structural equation modeling) to validate various dietary patterns and examine their associations with risk of type 2 diabetes, CVD, and total mortality in two large ongoing cohort studies, the Nurses' Health Study (n=121,700) and Health Professionals' Follow-up Study (n=51,529). In addition to evaluating prevailing dietary recommendations, we will also examine the role of the Mediterranean-type dietary pattern, the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, and the Atkins-type diet in predicting health outcomes. Using repeated measurements of diet, we will examine the impact of changes in eating patterns and diet quality over time on subsequent risk of diabetes, CVD, and total mortality. In addition, we will examine relationships between major dietary patterns and novel plasma biomarkers of inflammation and endothelial function and whether such relationships are mediated through obesity. Finally, we will test interactions between dietary patterns and individual SNPs and haplotypes of several promising candidate genes in the inflammation and endothelial dysfunction pathway on risk of CHD, including PPARalpha, PPARgamma, Adiponectin (AdipoQ), PON1, IL-6, TNF-alpha, ICAM-1, VCAM-1, E-Selectin, NOS3, ACE gene, and angiotensinogen (ANG) genes. Overall, the large size of these cohorts, the prospective design, the repeated and detailed measurements of diet and covariates, the high follow-up rates, and the availability of biochemical and DMA samples (most of analyses have already been funded) provide a unique opportunity to study the relationship between overall dietary patterns and the CVD, diabetes, and obesity in an extremely cost-efficient manner. We believe that this project presents a novel approach to study diet-disease relationship and will have important public health implications.